tbuckley/cabot-search huggingface dataset:
Analysis of bacterial vaginosis, the vaginal microbiome, and sexually transmitted infections following the provision of menstrual cups in Kenyan schools: Results of a nested study within a cluster randomized controlled trial
Authors: Supriya D. Mehta, Garazi Zulaika, Walter Agingu, Elizabeth Nyothach, Runa Bhaumik, Stefan J. Green, Anna Maria van Eijk, Daniel Kwaro, Fredrick Otieno, Penelope Phillips-Howard
Journal: PLoS Medicine (2023)

Background Nonhygienic products for managing menstruation are reported to cause reproductive tract infections. Menstrual cups are a potential solution. We assessed whether menstrual cups would reduce bacterial vaginosis (BV), vaginal microbiome (VMB), and sexually transmitted infections (STIs) as studies have not evaluated this. Methods and findings A cluster randomized controlled trial was performed in 96 Kenyan secondary schools, randomized (1:1:1:1) to control, menstrual cup, cash transfer, or menstrual cup plus cash transfer. This substudy assessing the impact of menstrual cups on BV, VMB, and STIs, included 6 schools from the control (3) and menstrual cup only (3) groups, both receiving BV and STI testing and treatment at each visit. Self-collected vaginal swabs were used to measure VMB (16S rRNA gene amplicon sequencing), BV (Nugent score), and STIs. STIs were a composite of Chlamydia trachomatis and Neisseria gonorrhoeae (nucleic acid amplification test) and Trichomonas vaginalis (rapid immunochromatographic assay). Participants were not masked and were followed for 30 months. The primary outcome was diagnosis of BV; secondary outcomes were VMB and STIs. Intention-to-treat blinded analyses used mixed effects generalized linear regressions, with random effects term for school. The study was conducted between May 2, 2018, and February 7, 2021. A total of 436 participants were included: 213 cup, 223 control. There were 289 BV diagnoses: 162 among control participants and 127 among intervention participants (odds ratio 0.76 [95% CI 0.59 to 0.98]; p = 0.038). The occurrence of Lactobacillus crispatus– dominated VMB was higher among cup group participants (odds ratio 1.37 [95% CI 1.06 to 1.75]), as was the mean relative abundance of L . crispatus (3.95% [95% CI 1.92 to 5.99]). There was no effect of intervention on STIs (relative risk 0.82 [95% CI 0.50 to 1.35]). The primary limitations of this study were insufficient power for subgroup analyses, and generalizability of findings to nonschool and other global settings. Conclusions Menstrual cups with BV and STI testing and treatment benefitted adolescent schoolgirls through lower occurrence of BV and higher L . crispatus compared with only BV and STI testing and treatment during the 30 months of a cluster randomized menstrual cup intervention. Trial registration ClinicalTrials.gov NCT03051789 .
Global prevalence of non-alcoholic fatty liver disease in type 2 diabetes mellitus: an updated systematic review and meta-analysis
Authors: Elina En Li Cho, Chong Zhe Ang, Jingxuan Quek, Clarissa Elysia Fu, Lincoln Kai En Lim, Zane En Qi Heng, Darren Jun Hao Tan, Wen Hui Lim, Jie Ning Yong, Rebecca Zeng, Douglas Chee, Benjamin Nah, Cosmas Rinaldi Adithya Lesmana, Aung Hlaing Bwa, Khin Maung Win, Claire Faulkner, Majd B Aboona, Mei Chin Lim, Nicholas Syn, Anand V. Kulkarni, Hiroyuki Suzuki, Hirokazu Takahashi, Nobuharu Tamaki, Karn Wijarnpreecha, Daniel Q. Huang, Mark Muthiah, Cheng Han Ng, Rohit Loomba
Journal: Gut (2023)

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, with type 2 diabetes mellitus (T2DM) as a major predictor. Insulin resistance and chronic inflammation are key pathways in the pathogenesis of T2DM leading to NAFLD and vice versa, with the synergistic effect of NAFLD and T2DM increasing morbidity and mortality risks. This meta-analysis aims to quantify the prevalence of NAFLD and the prevalence of clinically significant and advanced fibrosis in people with T2DM.MEDLINE and Embase databases were searched from inception until 13 February 2023. The primary outcomes were the prevalence of NAFLD, non-alcoholic steatohepatitis (NASH) and fibrosis in people with T2DM. A generalised linear mixed model with Clopper-Pearson intervals was used for the analysis of proportions with sensitivity analysis conducted to explore heterogeneity between studies.156 studies met the inclusion criteria, and a pooled analysis of 1 832 125 patients determined that the prevalence rates of NAFLD and NASH in T2DM were 65.04% (95% CI 61.79% to 68.15%, I2=99.90%) and 31.55% (95% CI 17.12% to 50.70%, I2=97.70%), respectively. 35.54% (95% CI 19.56% to 55.56%, I2=100.00%) of individuals with T2DM with NAFLD had clinically significant fibrosis (F2-F4), while 14.95% (95% CI 11.03% to 19.95%, I2=99.00%) had advanced fibrosis (F3-F4).This study determined a high prevalence of NAFLD, NASH and fibrosis in people with T2DM. Increased efforts are required to prevent T2DM to combat the rising burden of NAFLD.CRD42022360251.
The evolving landscape of salivary gland tumors
Authors: Conor E. Steuer, Glenn J. Hanna, Kartik Viswanathan, James E. Bates, Azeem S. Kaka, Nicole C. Schmitt, Alan L. Ho, Nabil F. Saba
Journal: CA A Cancer Journal for Clinicians (2023)

Abstract Salivary gland cancers are a rare, histologically diverse group of tumors. They range from indolent to aggressive and can cause significant morbidity and mortality. Surgical resection remains the mainstay of treatment, but radiation and systemic therapy are also critical parts of the care paradigm. Given the rarity and heterogeneity of these cancers, they are best managed in a multidisciplinary program. In this review, the authors highlight standards of care as well as exciting new research for salivary gland cancers that will strive for better patient outcomes.
Genetic and chemical targeting of the ATPase complex TIP48 and 49 impairs acute myeloid leukemia
Authors: Ayuna Hattori, Emi Takamatsu-Ichihara, Yoshiki Yamamoto, Shuhei Fujita, Kazutsune Yamagata, Takuo Katsumoto, Yukino Machida, Haruka Shinohara, Ryo Murakami, Issay Kitabayashi
Journal: Leukemia (2023)
RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer
Authors: Yi-Qun Li, Fang-Zhou Sun, Chun-Xiao Li, Hong-Nan Mo, Yan-Tong Zhou, Dan Lv, Jing-Tong Zhai, Hai-Li Qian, Fei Ma
Journal: Military Medical Research (2023)

Triple negative breast cancer (TNBC), the most aggressive subtype of breast cancer, is characterized by a high incidence of brain metastasis (BrM) and a poor prognosis. As the most lethal form of breast cancer, BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies. Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis (BCBrM), but the underlying mechanisms are far from being fully elucidated.Through analysis of BCBrM transcriptome data from mice and patients, and immunohistochemical validation on patient tissues, we identified and verified the specific down-regulation of retinoic acid receptor responder 2 (RARRES2), a multifunctional adipokine and chemokine, in BrM of TNBC. We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies. Key signaling pathway components were evaluated using multi-omics approaches. Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2.We found that down-regulation of RARRES2 is specifically associated with BCBrM, and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming. Mechanistically, reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue (PTEN)-mammalian target of rapamycin (mTOR)-sterol regulatory element-binding protein 1 (SREBP1) signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment.Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM. RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.
Metabolism, metabolites, and macrophages in cancer
Authors: Mengyuan Li, Yuhan Yang, Liting Xiong, Ping Jiang, Junjie Wang, Chunxiao Li
Journal: Journal of Hematology & Oncology (2023)

Abstract Tumour-associated macrophages (TAMs) are crucial components of the tumour microenvironment and play a significant role in tumour development and drug resistance by creating an immunosuppressive microenvironment. Macrophages are essential components of both the innate and adaptive immune systems and contribute to pathogen resistance and the regulation of organism homeostasis. Macrophage function and polarization are closely linked to altered metabolism. Generally, M1 macrophages rely primarily on aerobic glycolysis, whereas M2 macrophages depend on oxidative metabolism. Metabolic studies have revealed that the metabolic signature of TAMs and metabolites in the tumour microenvironment regulate the function and polarization of TAMs. However, the precise effects of metabolic reprogramming on tumours and TAMs remain incompletely understood. In this review, we discuss the impact of metabolic pathways on macrophage function and polarization as well as potential strategies for reprogramming macrophage metabolism in cancer treatment.
Understanding patch foraging strategies across development
Authors: Alex Lloyd, Essi Viding, Ryan McKay, Nicholas Furl
Journal: Trends in Cognitive Sciences (2023)

Patch foraging is a near-ubiquitous behaviour across the animal kingdom and characterises many decision-making domains encountered by humans. We review how a disposition to explore in adolescence may reflect the evolutionary conditions under which hunter-gatherers foraged for resources. We propose that neurocomputational mechanisms responsible for reward processing, learning, and cognitive control facilitate the transition from exploratory strategies in adolescence to exploitative strategies in adulthood - where individuals capitalise on known resources. This developmental transition may be disrupted by psychopathology, as there is emerging evidence of biases in explore/exploit choices in mental health problems. Explore/exploit choices may be an informative marker for mental health across development and future research should consider this feature of decision-making as a target for clinical intervention.
Why older adults can continue to benefit from covid-19 boosters
Authors: K Macartney
Journal: BMJ (2023)

Why older adults can continue to benefit from covid-19 boostersNewly published studies show that mRNA covid-19 boosters, including those updated against newer variants, are effective and safe in protecting older adults from severe covid-19, but what does that mean for healthcare providers and patients?Kristine Macartney and Bette Liu discuss Despite the covid-19 global health emergency being officially over, timely evidence is still needed on the safety and effectiveness of covid-19 vaccines.Most countries continue to recommend covid-19 vaccination for older adults to reduce the risk of severe disease. 1 Despite much of the population having "hybrid immunity," 2 derived from both vaccination and infection, covid-19 is still responsible for many hospital admissions and deaths among older people. 3 Data on the impact of additional vaccine doses, including those specifically designed to protect against new variants, is needed by policy makers, governments, and individuals to inform ongoing decision making.Uptake has declined recently, owing to complacency about the need for vaccines, 4 distrust fuelled by misinformation, concerns about safety, and the rolling back of delivery programmes.
Complex coacervate-derived hydrogel with asymmetric and reversible wet bioadhesion for preventing UV light-induced morbidities
Authors: Xin Peng, Yuan Li, Menghui Liu, Zhuo Li, Xuemei Wang, Kunyu Zhang, Xin Zhao, Gang Li, Liming Bian
Journal: Bioactive Materials (2023)

Protecting the skin from UV light irradiation in wet and underwater environments is challenging due to the weak adhesion of existing sunscreen materials but highly desired. Herein we report a polyethyleneimine/thioctic acid/titanium dioxide (PEI/TA/TiO2) coacervate-derived hydrogel with robust, asymmetric, and reversible wet bioadhesion and effective UV-light-shielding ability. The PEI/TA/TiO2 complex coacervate can be easily obtained by mixing a PEI solution and TA/TiO2 powder. The fluid PEI/TA/TiO2 coacervate deposited on wet skin can spread into surface irregularities and subsequently transform into a hydrogel with increased cohesion, thereby establishing interdigitated contact and adhesion between the bottom surface and skin. Meanwhile, the functional groups between the skin and hydrogel can form physical interactions to further enhance bioadhesion, whereas the limited movement of amine and carboxyl groups on the top hydrogel surface leads to low adhesion. Therefore, the coacervate-derived hydrogel exhibits asymmetric adhesiveness on the bottom and top surfaces. Moreover, the PEI/TA/TiO2 hydrogel formed on the skin could be easily removed using a NaHCO3 aqueous solution without inflicting damage. More importantly, the PEI/TA/TiO2 hydrogel can function as an effective sunscreen to block UV light and prevent UV-induced MMP-9 overexpression, inflammation, and DNA damage in animal skin. The advantages of PEI/TA/TiO2 coacervate-derived hydrogels include robust, asymmetric, and reversible wet bioadhesion, effective UV light-shielding ability, excellent biocompatibility, and easy preparation and usage, making them a promising bioadhesive to protect the skin from UV light-associated damage in wet and underwater environments.
Hemolysis dictates monocyte differentiation via two distinct pathways in sickle cell disease vaso-occlusion
Authors: Yunfeng Liu, Shan Su, Sarah Shayo, Weili Bao, Mouli Pal, Kai Dou, Patricia A. Shi, Banu Aygun, Sally Campbell-Lee, Cheryl A. Lobo, Avital Mendelson, Xiuli An, Deepa Manwani, Hui Zhong, Karina Yazdanbakhsh
Journal: Journal of Clinical Investigation (2023)

Sickle cell disease (SCD) is a hereditary hemoglobinopathy characterized by painful vaso-occlusive crises (VOC) and chronic hemolysis. The mononuclear phagocyte system is pivotal to SCD pathophysiology, but the mechanisms governing monocyte/macrophage differentiation remain unknown. This study examined the influence of hemolysis on circulating monocyte trajectories in SCD. We discovered that hemolysis stimulated CSF-1 production, partly by endothelial cells via Nrf2, promoting classical monocyte (CMo) differentiation into blood patrolling monocytes (PMo) in SCD mice. However, hemolysis also upregulated CCL-2 through IFN-I, inducing CMo transmigration and differentiation into tissue monocyte-derived macrophages. Blocking CMo transmigration by anti-P selectin antibody in SCD mice increased circulating PMo, corroborating that CMo-to-tissue macrophage differentiation occurs at the expense of CMo-to-blood PMo differentiation. We observed a positive correlation between plasma CSF-1/CCL-2 ratios and blood PMo levels in patients with SCD, underscoring the clinical significance of these two opposing factors in monocyte differentiation. Combined treatment with CSF-1 and anti-P selectin antibody more effectively increased PMo numbers and reduced stasis compared with single-agent therapies in SCD mice. Altogether, these data indicate that monocyte fates are regulated by the balance between two heme pathways, Nrf2/CSF-1 and IFN-I/CCL-2, and suggest that the CSF-1/CCL-2 ratio may present a diagnostic and therapeutic target in SCD.
pH-triggered dynamic erosive small molecule chlorambucil nano-prodrugs mediate robust oral chemotherapy
Authors: Xin Liu, Zhexiang Wang, Xiaodie Ren, Xinyang Chen, Jinjin Tao, Yuanhui Guan, Xuefeng Yang, Rupei Tang, Guoqing Yan
Journal: Asian Journal of Pharmaceutical Sciences (2023)

Currently, the dynamic erosive small molecule nano-prodrug is of great demand for oral chemotherapy, owing to its precise structure, high drug loading and improved oral bioavailability via overcoming various physiologic barriers in gastrointestinal tract, blood circulation and tumor tissues compared to other oral nanomedicines. Herein, this work highlights the successful development of pH-triggered dynamic erosive small molecule nano-prodrugs based on in vivo significant pH changes, which are synthesized via amide reaction between chlorambucil and star-shaped ortho esters. The precise nano-prodrugs exhibit extraordinarily high drug loading (68.16%), electric neutrality, strong hydrophobicity, and dynamic large-to-small size transition from gastrointestinal pH to tumoral pH. These favorable physicochemical properties can effectively facilitate gastrointestinal absorption, blood circulation stability, tumor accumulation, cellular uptake, and cytotoxicity, therefore achieving high oral relative bioavailability (358.72%) and significant tumor growth inhibition while decreasing side effects. Thus, this work may open a new avenue for robust oral chemotherapy attractive for clinical translation.
Exercise training and resting blood pressure: a large-scale pairwise and network meta-analysis of randomised controlled trials
Authors: Jamie J Edwards, Algis H P Deenmamode, Megan Griffiths, Oliver Arnold, Nicola J Cooper, Jonathan D Wiles, Jamie M O'Driscoll
Journal: British Journal of Sports Medicine (2023)

To perform a large-scale pairwise and network meta-analysis on the effects of all relevant exercise training modes on resting blood pressure to establish optimal antihypertensive exercise prescription practices.Systematic review and network meta-analysis.PubMed (Medline), the Cochrane library and Web of Science were systematically searched.Randomised controlled trials published between 1990 and February 2023. All relevant work reporting reductions in systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) following an exercise intervention of ≥2 weeks, with an eligible non-intervention control group, were included.270 randomised controlled trials were ultimately included in the final analysis, with a pooled sample size of 15 827 participants. Pairwise analyses demonstrated significant reductions in resting SBP and DBP following aerobic exercise training (-4.49/-2.53 mm Hg, p<0.001), dynamic resistance training (-4.55/-3.04 mm Hg, p<0.001), combined training (-6.04/-2.54 mm Hg, p<0.001), high-intensity interval training (-4.08/-2.50 mm Hg, p<0.001) and isometric exercise training (-8.24/-4.00 mm Hg, p<0.001). As shown in the network meta-analysis, the rank order of effectiveness based on the surface under the cumulative ranking curve (SUCRA) values for SBP were isometric exercise training (SUCRA: 98.3%), combined training (75.7%), dynamic resistance training (46.1%), aerobic exercise training (40.5%) and high-intensity interval training (39.4%). Secondary network meta-analyses revealed isometric wall squat and running as the most effective submodes for reducing SBP (90.4%) and DBP (91.3%), respectively.Various exercise training modes improve resting blood pressure, particularly isometric exercise. The results of this analysis should inform future exercise guideline recommendations for the prevention and treatment of arterial hypertension.
Artificial Sweeteners and Risk of Type 2 Diabetes in the Prospective NutriNet-Santé Cohort
Authors: Charlotte Debras, Mélanie Deschasaux-Tanguy, Eloi Chazelas, Laury Sellem, Nathalie Druesne-Pecollo, Younes Esseddik, Fabien Szabo de Edelenyi, Cédric Agaësse, Alexandre De Sa, Rebecca Lutchia, Chantal Julia, Emmanuelle Kesse-Guyot, Benjamin Allès, Pilar Galan, Serge Hercberg, Inge Huybrechts, Emmanuel Cosson, Sopio Tatulashvili, Bernard Srour, Mathilde Touvier
Journal: Diabetes Care (2023)

OBJECTIVE To study the relationships between artificial sweeteners, accounting for all dietary sources (total and by type of artificial sweetener) and risk of type 2 diabetes (T2D), in a large-scale prospective cohort. RESEARCH DESIGN AND METHODS The analyses included 105,588 participants from the web-based NutriNet-Santé study (France, 2009–2022; mean age 42.5 ± 14.6 years, 79.2% women). Repeated 24-h dietary records, including brands and commercial names of industrial products, merged with qualitative and quantitative food additive composition data, enabled artificial sweetener intakes to be accurately assessed from all dietary sources. Associations between artificial sweeteners (total, aspartame, acesulfame potassium [K], and sucralose) and T2D were investigated using Cox proportional hazard models adjusted for potential confounders, including weight variation during follow-up. RESULTS During a median follow-up of 9.1 years (946,650 person-years, 972 incident T2D), compared with nonconsumers, higher consumers of artificial sweeteners (i.e., above the sex-specific medians of 16.4 mg/day in men and 18.5 mg/day in women) had higher risks of developing T2D (hazard ratio [HR] 1.69; 95% CI 1.45–1.97; P-trend &amp;lt;0.001). Positive associations were also observed for individual artificial sweeteners: aspartame (HR 1.63 [95% CI 1.38–1.93], P-trend &amp;lt;0.001), acesulfame-K (HR 1.70 [1.42–2.04], P-trend &amp;lt;0.001), and sucralose (HR 1.34 [1.07–1.69], P-trend = 0.013). CONCLUSIONS Potential for reverse causality cannot be eliminated; however, many sensitivity analyses were computed to limit this and other potential biases. These findings of positive associations between artificial sweetener intakes and increased T2D risk strengthen the evidence that these additives may not be safe sugar alternatives. This study provides important insights in the context of on-going reevaluation of artificial sweeteners by health authorities worldwide.
Correction: Large-scale real-life analysis of survival and usage of therapies in multiple myeloma
Authors: N Lopez-Muñoz, G Hernández-Ibarburu, R Alonso, J M Sanchez-Pina, R Ayala, M Calbacho, C Cuellar, M T Cedena, A Jiménez-Ubieto, R Iñiguez, M Pedrera, J Cruz, L Meloni, D Pérez-Rey, P Serrano, J de la Cruz, J Martinez-Lopez
Journal: Journal of Hematology & Oncology (2023)
Immunosuppressed Pets as a Conduit for Zoonotic Tuberculosis
Authors: Ciara Ottewill, Lorraine Dolan, Esther López Bailén, Emma Roycroft, Margaret Fitzgibbon, Emer O. Donohue, Anne Marie McLaughlin, Guy McGrath, Joseph Keane
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Immunosuppressed Pets as a Conduit for Zoonotic Tuberculosis." American Journal of Respiratory and Critical Care Medicine, 208(6), pp. 732–733